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Overlapping Region of p53/Wrap53 Transcripts: Mutational Analysis and Sequence Similarity with microRNA-4732-5p

  • Pouladi, Nasser (Department of Cellular and Molecular Biology, School of Biology, College of Sciences, University of Tehran) ;
  • Kouhsari, Shideh Montasser (Department of Cellular and Molecular Biology, School of Biology, College of Sciences, University of Tehran) ;
  • Feizi, Mohammadali Hosseinpour (Department of Biology, Faculty of Natural Science, University of Tabriz) ;
  • Gavgani, Reyhaneh Ravanbakhsh (Department of Biology, Faculty of Natural Science, University of Tabriz) ;
  • Azarfam, Parvin (Department of Biology, Faculty of Natural Science, University of Tabriz)
  • Published : 2013.06.30

Abstract

Background: Although the majority of investigations concerned with TP53 and its protein have focused on coding regions, recently a set of studies highlighted significant roles of regulatory elements located in p53 mRNA, especially 5'UTR. The wrap53${\alpha}$ transcript is one of those that acts as a natural antisense agent, forming RNA-RNA hybrids with p53 mRNA and protecting it from degradation. Materials and Methods: In this study, we focused on the mutation status of exon $1{\alpha}$ of the WRAP53 gene (according to exon 1 of p53) in 160 breast tumor tissue samples and conducted a bioinformatics search for probable miRNA binding site in the p53/wrap53 overlapping region. Mutations were detected, using single stranded conformation polymorphism (SSCP) and sequencing. We applied the miRBase database for prediction of miRNAs which target overlapping region of p53/wrap53 transcripts. Results: Our results showed all samples to have wild type alleles in exon 1 of TP53 gene. We could detect a novel and unreported intronic mutation (IVS1+56, G>C) outside overlapping regions of p53/wrap53 genes in breast cancer tissues and also predict the presence of a binding site for miR-4732-5p in the 5'UTR of Wrap53 mRNA. Conclusions: From our findings we propose designing further studies focused on overexpression of miRNA-4732-5p and introducing different mutations in the overlapping region of wrap53 and p53 genes in order to study their effects on p53 and its ${\Delta}N$ isoform (${\Delta}$40p53) expression. The results may provide new pieces in the p53 targeting puzzle for cancer therapy.

Keywords

p53;wrap53;miRNA-4732-5p;mutation;5' UTR;cancer

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